Aerolate

Action

Relaxes bronchial smooth muscles, suppressing airway response to stimuli. Also inhibits phosphodiesterase and release of slow-reacting substance of anaphylaxis and histamine.

Availability

Capsules (immediate-release): 100 mg, 200 mg

Capsules (extended-release, 8 to 12 hours): 50 mg, 60 mg, 65 mg, 75 mg, 100 mg, 125 mg, 130 mg

Capsules (extended-release, 12 hours): 50 mg, 125 mg, 130 mg, 250 mg, 260 mg

Capsules (extended-release, 24 hours): 100 mg, 200 mg, 300 mg, 400 mg

Elixir: 80 mg/15 ml

Injection (with dextrose): 0.4 mg/ml, 0.8 mg/ml, 1.6 mg/ml, 2 mg/ml, 3.2 mg/ml, 4 mg/ml

Syrup (cherry): 80 mg/15 mg, 150 mg/15 ml

Tablets (immediate-release): 100 mg, 125 mg, 200 mg, 250 mg, 300 mg

Tablets (extended-release, 12 to 24 hours): 100 mg, 200 mg, 300 mg, 400 mg, 450 mg, 600 mg

Tablets (extended-release, 24 hours): 400 mg, 600 mg

Indications and dosages

➣ Acute bronchospasm in patients not receiving theophylline

Adults (otherwise healthy nonsmokers): Initially, 6 mg/kg P.O., followed in next 12 to 16 hours by 3 mg/kg P.O. q 6 hours for two doses, then a maintenance dosage of 3 mg/kg P.O. q 8 hours

Children ages 9 to 16; young adult smokers: Initially, 6 mg/kg P.O., followed in next 12 to 16 hours by 3 mg/kg P.O. q 4 hours for three doses, then a maintenance dosage of 3 mg/kg P.O. q 6 hours

Children ages 1 to 9: Initially, 6 mg/kg P.O., followed in next 12 to 16 hours by 4 mg/kg P.O. q 4 hours for three doses, then a maintenance dosage of 4 mg/kg P.O. q 6 hours

➣ Acute bronchospasm in patients receiving theophylline

Adults and children: Loading dose based partly on time, amount, and administration route of last dose and on expectation that each 0.5 mg/kg will produce 1 mcg/ml rise in theophylline blood level. In significant respiratory distress, loading dose may be 2.5 mg/kg P.O. or I.V. to increase theophylline level by approximately 5 mcg/ml.

➣ Chronic bronchospasm

Adults and children: Immediate-release forms-16 mg/kg or 400 mg P.O. daily (whichever is lower) in three to four divided doses q 6 to 8 hours. Timed-release forms-12 mg/kg or 400 mg P.O. daily (whichever is lower) in three to four divided doses q 8 to 12 hours. May increase dosage of either immediate- or timed-release form at 2- to 3-day intervals, to a maximum of 13 mg/kg or 900 mg daily (whichever is lower) in patients older than age 16, 18 mg/kg daily in children ages 12 to 16, 20 mg/kg daily in children ages 9 to 12, or 24 mg/kg daily in children up to age 9.

Dosage adjustment

• Cor pulmonale or heart failure

• Elderly patients

• Young adults

Off-label uses

• Essential tremor

• Apnea and bradycardia in premature infants

Contraindications

• Hypersensitivity to drug or other xanthines (such as coffee, theobromine)

• Active peptic ulcer

• Seizure disorder

Precautions

Use cautiously in:

• alcoholism; heart failure or other cardiac or circulatory impairment; hypertension; renal or hepatic disease; COPD; hypoxemia; hyperthyroidism; diabetes mellitus; glaucoma; peptic ulcer disease

• elderly patients

• children younger than age 1.

Administration

• For I.V. delivery, use infusion solution designed for drug, or mix with dextrose 5% in water. Administer by controlled infusion pump.

• Know that for acute bronchospasm, theophylline preferably is given I.V. as 20 mg/ml of theophylline (or 25 mg/ml of aminophylline).

• Don't give timed-release form to patient with acute bronchospasm.

Adverse reactions

CNS: irritability, dizziness, nervousness, restlessness, headache, insomnia, reflex hyperexcitability, seizures

CV: palpitations, marked hypotension, sinus tachycardia, extrasystole, circulatory failure, ventricular arrhythmias

GI: nausea, vomiting, diarrhea, hematemesis, gastroesophageal reflux

GU: increased diuresis, proteinuria

Metabolic: hyperglycemia, syndrome of inappropriate antidiuretic hormone secretion

Musculoskeletal: muscle twitching

Respiratory: tachypnea, respiratory arrest

Skin: urticaria, rash, alopecia, flushing

Other: fever, hypersensitivity reaction

Interactions

Drug-drug. Allopurinol, calcium channel blockers, cimetidine, corticosteroids, disulfiram, ephedrine, hormonal contraceptives, influenza virus vaccine, interferon, macrolides, mexiletine, nonselective beta-adrenergic blockers, quinolones, thiabendazole: increased theophylline blood level, greater risk of toxicity

Aminoglutethimide, barbiturates, ketoconazole, rifampin, sulfinpyrazone, sympathomimetics: decreased theophylline blood level and effects

Carbamazepine, isoniazid, loop diuretics: increased or decreased theophylline blood level

Halothane: increased risk of arrhythmias

Hydantoins: decreased hydantoin blood level

Lithium: decreased therapeutic effect of lithium

Nondepolarizing muscle relaxants: reversal of neuromuscular blockade

Propofol: antagonism of propofol's sedative effects

Tetracyclines: increased risk of adverse reactions to theophylline

Drug-diagnostic tests. Glucose: increased level

Drug-food. Any food: altered bioavailability and absorption of some timed-release theophylline forms, causing rapid release and possible toxicity

Caffeine- or xanthine-containing foods and beverages: increased theophylline blood level and greater risk of adverse CNS and cardiovascular reactions

Diet high in protein and charcoal-broiled beef and low in carbohydrates: increased theophylline elimination, decreased efficacy

High-carbohydrate, low-protein diet: decreased theophylline elimination, increased risk of adverse reactions

Drug-herbs. Caffeine-containing herbs (such as cola nut, guarana, maté): increased theophylline blood level, greater risk of adverse CNS and cardiovascular reactions

Ephedra (ma huang): increased stimulant effect

St. John's wort: decreased theophylline blood level and efficacy

Drug-behaviors. Nicotine (in cigarettes, gum, transdermal patches): increased theophylline metabolism, decreased efficacy

Patient monitoring

• Monitor for signs and symptoms of hypersensitivity reaction, including rash and fever.

• Assess respiratory status. Monitor pulmonary function tests to gauge drug efficacy and identify adverse effects.

• Monitor cardiovascular and neurologic status carefully.

• Assess glucose level in diabetic patient.

Patient teaching

• Advise patient to take oral form with 8 oz of water 1 hour before or 2 hours after meals.

• Tell patient not to crush or chew timed-release form.

• Caution patient not to use different drug brands interchangeably.

Instruct patient to immediately report worsening dyspnea and other respiratory problems.

• Teach patient to recognize and report adverse neurologic reactions.

• Tell patient that all nicotine forms (including cigarettes, patches, and gum) decrease drug efficacy. Discourage nicotine use.

• Advise patient that a diet high in protein and charcoal-broiled beef and low in carbohydrates makes drug less effective.

• Tell patient that a high-carbohydrate, low-protein diet increases risk of adverse reactions, as do products containing caffeine.

• Caution patient to avoid herbs, especially ephedra and St. John's wort.

• Advise patient not to take over-the-counter drugs without prescriber's approval. Tell him to inform all prescribers he's taking drug, because it interacts with many other drugs.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, herbs, and behaviors mentioned above.